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Five questions for Steven Hyman

Steven E. Hyman is intent on reinventing himself in a place that welcomes creativity.

Former provost of Harvard University and before that, director of the National Institute of Mental Health (NIMH), the Harvard University professor of stem cell and regenerative biology began a one-year sabbatical at the Broad Institute in July. He is a scholar in residence at the Stanley Center for Psychiatric Research within the Broad’s Psychiatric Disease Program.

On the eve of a trip to participate in a meeting on neuropsychiatric disorders in sub-Saharan Africa at the Mbarara University of Science and Technology in Uganda, followed by visiting Partners In Health sites and a meeting with the Health Minister in Rwanda, he answered our five questions about his new role.

Q1: After 10 years in which you aimed to knit together the highly decentralized Harvard, how did you choose the Broad for your next act?

SH: There are a small number of organizations in the Boston area that have the characteristics of being problem-oriented and importantly, cross-disciplinary, cross-institutional, and in some sense, cross-sector. By “cross-sector,” I mean they connect universities, hospitals, and welcome private sector collaboration. I think this is the kind of setting that is conducive to creativity and innovation. The Broad is to date, arguably, the most advanced of these relatively new kinds of organizations, which also include the Wyss Institute for Biologically Inspired Engineering and, in a more virtual way, the Harvard Stem Cell Institute.

This seemed like the ideal place to come and to try to “rehabilitate myself,” or better, to reinvent myself after 10 years as Harvard provost and before that, six years in U.S. government as NIMH director — with one day off between those two jobs. It’s reinvention in a place that welcomes risk-taking. I recognize that I’m in a position to take substantial risks. I don’t have to worry about my next paper or, for that matter, my career. It already is what it is, right? So it’s terrific to be in a place where there isn’t a cookie-cutter approach to how one does science.

Q2: What will you focus on at the Broad?

SH: I’m not quite sure yet, but I am spending a lot of time figuring that out. In truth I have to begin by finding out whether I can be a significant contributor to the doing of science, especially applying the Broad’s strengths to neuroscience and to the development of desperately needed new treatments for brain disorders. It’s possible that my years in administration have been so cognitively ruinous to me that I should just go off and run something again. But I fell down the administrative well too early in life and I feel a hunger to re-engage with the doing of science. I became NIMH director at 43. Now I’m 59.

I joke, of course. My leadership roles felt like real and significant contributions, but in my quiet moments I kept thinking about science, and feeling frustration about the near standstill in developing new treatments for neuropsychiatric disorders.

Q3: What can the Broad bring to neuroscientific research?

SH: While it’s still early days, I think genetics is going to provide some of the first really useful clues to the biology of neuropsychiatric disorders – in particular, autism, schizophrenia, and bipolar disorder. The question will soon become: How are we going to put genetic discoveries to work? Over time, we have to figure our how to create truly informative animal models. That task remains largely unaccomplished.

Q4: Can you give an example of a new approach?

SH: One very interesting possibility to me, already begun at the Broad, is to see whether one can use stem cell technologies, especially iPS [induced pluripotent stem] cells as therapeutic screens. Perhaps we can “convince” iPS cells to recapitulate simple circuits on chips, thus increasing the power of the technology to answer important questions.

Ultimately, I believe we will be able to combine genetics and information from genetic animal models with human neuroimaging and cognitive neuroscience to develop a reasonable understanding of the molecules, cells, and circuits involved in the pathogenesis of neuropsychiatric disorders. But that will take a long time. For the whole cluster of disorders that go by the anachronistic misnomer of “mental disorders,” there haven’t been any fundamentally new approaches to treatment in more than half a century. We really have to do better.

Q5: Why is “mental disorder” a misnomer?

SH: Although René Descartes has been dead for more than 300 years, his radical separation of mind from body continues to plague us. If you call something a “mental” disorder, where’s the brain in that? And in some ways it feeds into stigma because if something is conceptualized as purely mental, well, why can’t you just will it away?

On the other hand, if you forget about the mind, you’re also doing an injustice to the people with these disorders because they have a profound influence on lived experience and subjectivity. Ultimately when we ask what goes wrong to produce neuropsychiatric disorders, we need to answer in terms of molecules, cells, and circuits if we are going to be able to design therapies. Even psychotherapies work by producing neural plasticity. But we should not ignore or deny the experience of the affected individuals. Pathogenesis comes, in different measures for different disorders, from a combination of “bottom-up” biological actors such as genes, epigenetic marks, and stochastic influences with “top down” influences such as diverse aspects of the environment, including lived experience. The whole point of having a human brain, pace Descartes, is to learn and to adapt, and to record the results of experience in this biological organ.

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joanpendleton, August 21, 2012

Der Dr Hyman,
I am being presumptuous and apologies in advance: Why is there no researcher who has set out to investigate Irish schizophrenia as in Ireland and among Irish immigrants in US you will find the highest rate of the illness in the world- highest rates ever recorded. Head of the Nile maybe? Please someone. Nile>look into this? look into this

Elizabeth Cooney, August 21, 2012

Thanks for your comment -- we've shared it with our colleagues in the Stanley Center. If they have additional information, we will either share it here or send you a private message.

Elizabeth Cooney, August 22, 2012

More information from the Stanley Center: We are collaborating with Kenneth Kendler, who has a longstanding study of schizophrenia in the Republic of Ireland and in Northern Ireland. His studies include the Roscommon Family Study. His major collaborators at the Stanley Center are Steve McCarroll, Mark Daly, and Ben Neale.